1/25/2024 0 Comments Irip antibodyExcessive fibrosis, degeneration and loss of cardiomyocytes have been involved in this pathological process ( 9– 11). Heart failure caused by these diseases further promotes abnormal myocardial remodeling, which in turn exacerbates heart failure to form a vicious circle ( 8). Acquisition of cardiac homeostasis needs normal specific cellular-molecular mechanisms and coordinated intercellular interactions which could be interfered by persistent and harmful external environmental stimuli such as overload, myocardial ischemia, leading to pathological tissue remodeling deviating from homeostasis and causing various cardiac diseases such as ischemic cardiomyopathy, hypertrophic cardiomyopathy, atrial fibrillation and other arrhythmias ( 4– 7). Maintenance of normal cardiac function requires fine-tune regulation of myocardial homeostasis that enables the heart to self-adjust under physiological stress and volume load to produce physiological hypertrophic responses and compensatory growth, thus playing a key role in the cardiac development and stress response ( 1– 3). Deeper structural and functional analysis will be helpful to enrich the regulatory network of cardiac remodeling and to identify potential therapeutic targets. Finally, the expression of CKAP4 is down-regulated in human remodeling fibrotic atrium.Ĭonclusions: We reveal certain RNA-binding features of CKAP4 suggesting a relevant role as an unconventional RNA-binding protein in cardiac remodeling process. Furthermore, qPCR verified CKAP4 differentially bound lncRNAs including LINC00504, FLJ22447, RP11-326N17.2, and HELLPAR in remodeling myocardial tissues when compared with normal myocardial tissues. More impressively, peak analysis revealed the lncRNA-binding features of CKAP4 in both IP groups. The signal pathways ranking most varied in the IP2 group compared to the IP1 group were relating to mitotic cell cycle, protein ubiquitination and nerve growth factor receptors. Binding peak-related gene cluster enrichment analysis demonstrated these genes were mainly involved in biological processes such as signal transduction, protein phosphorylation, axonal guidance, and cell connection. The top five binding motifs were obtained by HOMER, in which GGGAU was the binding sequence that appeared simultaneously in both IP groups. There were 913 overlapping binding peaks between the IP1 and IP2 groups. By statistically analyzing the distribution of binding peaks in various regions on the reference human genome, we found that the reads of IP samples were mainly distributed in the intergenic and intron regions implying that CKAP4 is more inclined to combine non-coding RNAs. Results: iRIP-seq was successfully performed, CKAP4-bound RNAs were characterized. Quantitative PCR and Western blotting were applied to identify CKAP4 mRNA and protein expression levels in human right atrium samples. Using improved RNA immunoprecipitation and sequencing (iRIP-seq), we sought to analyze the RNAs bound by CKAP4 in normal atrial muscle (IP1 group) and remodeling fibrotic atrial muscle (IP2 group) from patients with cardiac valvular disease. Methods: We assumed that CKAP4 held a role in the regulation of cardiac fibrotic remodeling as an RNA-binding protein. As one of cardiac activated-myofibroblast protein markers, CKAP4 may be involved in this process and the mechanisms have not been explored. 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Chinaīackground: Pathological tissue remodeling such as fibrosis is developed in various cardiac diseases.1Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha, China.Hong Zhu 1,2, Yanfeng Zhang 1,2, Chengliang Zhang 1,2 and Zhongshang Xie 1,2 *
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